United States-Based Colorectal Cancer Surgical Trials Lack Representation and Adequate Reporting of Racially and Ethnically Diverse Participants: Systematic Review and Regression Analysis.

BACKGROUND: Despite the established National Institute of Health Revitalization Act, which aims to include ethnic and racial minority representation in surgical trials, racial and ethnic enrollment disparities persist. OBJECTIVE: To assess the proportion of patients from minority races and ethnicities that are included in colorectal cancer surgical trials and reporting characteristics. DATA SOURCES: Search was performed using MEDLINE (Ovid), Embase, Web of Science, and Cochrane Central. STUDY SELECTION: Inclusion criteria included 1) trials performed in the United States between January 1, 2000, and May 30, 2022; 2) patients with colorectal cancer diagnosis; and 3) surgical intervention, technique, or postoperative outcome. Trials evaluating chemotherapy, radiotherapy, or other nonsurgical interventions were excluded. INTERVENTIONS: Pooled proportion and regression analysis was performed to identify the proportion of patients by race and ethnicity included in surgical trials and the association of year of publication and funding source. MAIN OUTCOME MEASURES: Proportion of trials reporting race and ethnicity and proportion of participants by race and ethnicity included in surgical trials. RESULTS: We screened 10,673 unique publications, of which 80 were examined in full text. Fifteen studies met our inclusion criteria. Ten (66.7%) trials did not report race, 3 reported races as a proportion of White participants only, and 3 reported 3 or more races. There was no description of ethnicity in 11 (73.3%) trials, with 2 describing "non-Caucasian" as ethnicity and 2 describing only Hispanic ethnicity. Pooled proportion of White participants was 81.3%, of Black participants was 6.2%, of Asian participants was 3.6%, and of Hispanic participants was 3.5%. LIMITATIONS: A small number of studies was identified that reported racial or ethnic characteristics of their participants. CONCLUSIONS: Both race and ethnicity are severely underreported in colorectal cancer surgical trials. To improve outcomes and ensure the inclusion of vulnerable populations in innovative technologies and novel treatments, reporting must be closely monitored.

Developing messages to encourage healthy, sustainable dietary substitutions: A qualitative study with US emerging adults.

Prior research shows that adopting simple dietary substitutions (e.g., replacing beef with poultry or plant-based entrees) can improve dietary quality and reduce the negative environmental consequences of food production, but little is known about how to encourage people to adopt these substitutions. This study aimed to examine reactions to messages encouraging healthy, sustainable dietary substitutions among emerging adults ages 18-25. We conducted four online focus groups with a diverse sample of US emerging adults (n = 28; 61% female). Focus groups explored emerging adults' reactions to messages encouraging them to adopt three target dietary substitutions: replacing beef and pork with poultry and plant-based entrees; replacing juice with whole fruit; and replacing dairy milk with non-dairy milk. We transcribed discussions verbatim and adopted a thematic approach to analyzing the transcripts. Results showed that participants perceived messages to be most effective at encouraging the target dietary substitutions when the messages: encouraged specific, achievable dietary changes; linked these dietary changes to clear consequences; included personally relevant content; included statistics; were succinct; and used a positive tone. Across the target dietary substitutions, two message topics (small changes, big benefits, which emphasized how small dietary changes can have large positive health and environmental impacts, and warning, which discussed the negative health and environmental impacts of dietary choices) were generally perceived to be most effective. A few participants expressed doubt that the target dietary substitutions would have meaningful environmental impacts. Results suggest that campaign messages to encourage healthy, sustainable dietary substitutions may be more effective if the messages make the target dietary substitutions seem achievable and use statistics to clearly describe the positive impacts of making these changes.

Examining the effects of brand and licensed characters on parents' perceptions of Children's breakfast cereals.

Brand and licensed characters frequently appear on children's breakfast cereal boxes and are known to affect children's product perceptions, selection, and consumption. However, less is known about their impact on parents' perceptions of foods they purchase for their child. The present study assessed the impact of brand and licensed characters featured on three children's breakfast cereal packages on parents' intentions and perceptions in an online experiment. Parents of children aged 2-12 years (n = 1013) were randomized into one of two conditions: breakfast cereals containing brand and licensed characters or breakfast cereals without any characters. Within each condition, participants viewed three breakfast cereal brands in random order per their assigned condition and reported their purchase intentions, healthfulness perceptions, and perceptions of appeal to children using 5-point Likert scales. No significant differences in purchase intentions (p = 0.91), perceived healthfulness (p = 0.52) or perceived child appeal (p = 0.59) were observed between the experimental and control groups. However, exploratory moderation analyses revealed that educational attainment moderated the impact of experimental condition on purchase intentions (p for interaction = 0.002) such that participants with a bachelor's degree in the character condition reported 0.36 points lower purchase intentions compared to the control with no difference between conditions for those with an associate's degree/trade school or high school degree or less. This study did not find an impact of brand and licensed characters on children's breakfast cereals, suggesting that their primary appeal is directly to children. Parents with higher educational attainment may be skeptical of characters on cereal brands. Additional research on the impact of brand and licensed characters on other products, in real-world settings, is needed.

Evidence-based review of nonantibiotic urinary tract infection prevention strategies for women: a patient-centered approach.

PURPOSE OF REVIEW: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence. RECENT FINDINGS: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d -mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality. SUMMARY: There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.

Sulfonamide Porphyrins as Potent Photosensitizers against Multidrug-Resistant Staphylococcus aureus (MRSA): The Role of Co-Adjuvants.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 µM upon white light radiation with an irradiance of 25 mW cm-2 and a total light dose of 15 J cm-2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

Current Photoactive Molecules for Targeted Therapy of Triple-Negative Breast Cancer.

Cancer is the second leading cause of death worldwide; therefore, there is an urgent need to find safe and effective therapies. Triple-negative breast cancer (TNBC) is diagnosed in ca. 15-20% of BC and is extremely aggressive resulting in reduced survival rate, which is mainly due to the low therapeutic efficacy of available treatments. Photodynamic therapy (PDT) is an interesting therapeutic approach in the treatment of cancer; the photosensitizers with good absorption in the therapeutic window, combined with their specific targeting of cancer cells, have received particular interest. This review aims to revisit the latest developments on chlorin-based photoactive molecules for targeted therapy in TNBC. Photodynamic therapy, alone or combined with other therapies (such as chemotherapy or photothermal therapy), has potential to be a safe and a promising approach against TNBC.

Cationic Pyrrolidine/Pyrroline-Substituted Porphyrins as Efficient Photosensitizers against E. coli.

New porphyrin-pyrrolidine/pyrroline conjugates were prepared by revisiting 1,3-dipolar cycloaddition reactions between a porphyrinic azomethine ylide and a series of dipolarophiles. Cationic conjugates obtained by alkylation of the pyrrolidine/pyrroline cycloadducts showed ability to generate singlet oxygen and to produce iodine in presence of KI when irradiated with visible light. Some of the cationic derivatives showed photobactericidal properties towards a Gram-negative bioluminescent E. coli. In all cases, these features were significantly improved using KI as coadjutant, allowing, under the tested conditions, the photoinactivation of the bacterium until the detection limit of the method with a drastic reduction of the required photosensitizer concentration and irradiation time. The obtained results showed a high correlation between the ability of the cationic porphyrin derivative to produce singlet oxygen and iodine and its E. coli photoinactivation profile.

Association between race and treatment patterns and survival outcomes in multiple myeloma: A Connect MM Registry analysis.

BACKGROUND: Studies have reported racial disparities in access to and use of multiple myeloma (MM) treatments between African American (AA) and White patients. Although AA patients demonstrate longer disease-specific survival, this has not uniformly translated into improved survival over time. The association between race and treatment patterns and survival outcomes was analyzed using data from the Connect MM Registry. METHODS: The Connect MM Registry is a large US, multicenter, prospective observational cohort study of patients with newly diagnosed MM. Patients who received first-line (1L) stem cell transplantation (SCT) or who did not receive SCT (non-SCT or non-stem cell transplantation [NSCT]) were grouped by raceEffects of race and transplantation status on the use of triplet treatment were estimated using logistic regression. RESULTS: Treatment patterns in 1L (types and duration of induction, posttransplantation maintenance) were similar between AA and White patients. SCT rates in 1L (32% vs 36%) and triplet treatment use (AA: 44% for NSCT patients and 72% for SCT patients; and White: 48% for NSCT patients and 72% for SCT patients) during first induction were similar. No significant effect of race or transplantation status on 1L triplet treatment use was observed. Race was not found to be associated with survival outcomes among patients who underwent NSCT; however, AA patients who received SCT had significantly longer overall survival compared with White patients who underwent SCT (not reached vs 88.2 months; hazard ratio, 0.56; 95% CI, 0.35-0.89 [P = .0141]). CONCLUSIONS: AA and White patients were found to have similar treatment patterns in the Connect MM Registry, suggesting that both groups had equal access to health care. In this real-world setting, AA patients received standard-of-care treatment, which might have contributed to better MM-specific survival compared with White patients.

Impact of hospital volume on patient safety indicators and failure to rescue following open aortic aneurysm repair.

OBJECTIVE: Failure to rescue (FTR), a patient safety indicator (PSI) defined, codified, and adjudicated by the Agency for Healthcare Research and Quality, is classified as a preventable inpatient death following major complications. FTR has been reported to be a significant driver of postoperative mortality after open abdominal aortic aneurysm (OAAA) repair. The association between hospital volume (HV) and mortality is well known; however, the mechanisms responsible for these improved outcomes and relative contribution to observed interhospital variation is poorly understood. Similarly, HV influence on specific complications predictive of FTR is unknown; therefore, we sought to determine how HV influences risk and contributes to interhospital variation in PSI events leading to FTR and/or in-hospital mortality after OAAA repair. METHODS: The Vizient database (174 academic/nonacademic hospitals) was queried for all OAAA repairs (elective, n = 2827; nonelective, n = 1622) completed from 2012 to 2014. The primary endpoint was combined FTR and/or in-hospital 30-day mortality. Risk-adjusted rates of complications, Agency for Healthcare Research and Quality-designated PSIs, and FTR were determined. Additional modeling identified PSIs associated with FTR, whereas HV effects on PSIs and FTR were evaluated using mixed-effect models accounting for interhospital variation. Proportion of variation attributable to HV was estimated by contrasting hospital random effect variances in the presence/absence of volume effects. RESULTS: The combined overall FTR/in-hospital 30-day mortality rate was 9.3% (n = 414). For elective and nonelective cases, the overall FTR and 30-day mortality rates were: FTR, 1.6%, 4.9%; and 30-day in-hospital mortality, 3.4%, 17.5%, respectively. HV significantly influenced FTR/30-day in-hospital mortality (P < .0001). FTR/30-day mortality odds for hospitals with 3-year volumes of 50, 100, 150, and 200 cases were 1.4, 2.0, 2.7, and 3.0 times lower, respectively, than hospitals performing ≤25 cases/3 years. The proportion of interhospital variation attributed to HV was greatest for FTR/30-day mortality (62%). Procedural volume accounted for 41% and 38% of interhospital variation in postoperative bleeding and myocardial infarction, respectively. Preoperative predictors of FTR included coagulopathy, arrhythmia (nonelective cases); congestive heart failure, obesity (elective cases); and age, neurological disease, hypertension, and valvular disease (all cases). CONCLUSIONS: OAAA FTR/30-day in-hospital mortality strongly correlated with annual case volume with higher volume centers having the lowest risk. Notably, HV accounted for a significant proportion of the observed variation in FTR and specific complications providing direct evidence for how the volume-outcome relationship may influence perioperative mortality. These findings can inform stakeholders to strategically enable them to implement processes of care directed at the most vulnerable patients that are designed to reduce the likelihood of preventable adverse events and death after OAAA repair. Furthermore, these results underscore the need to regionalize OAAA repair and potentially other complex operations, to HV centers because of their improved ability to rescue patients experiencing complications associated with postoperative mortality.

An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay.

Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5'UTR/Npro, Npro and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10-3 substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development.

New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties.

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.

Development of a prognostic model for overall survival in multiple myeloma using the Connect® MM Patient Registry.

Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect® MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2012-2016) of 3011 patients with NDMM, we identified prognostic variables for OS via the multivariable analysis of baseline patient characteristics in Cohort 1 (n = 1493) and developed a tool to examine individual outcomes. Factors associated with OS (n = 1450 treated patients; P < 0·05) were age, del(17p), triplet therapy use, EQ-5D mobility, International Staging System stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status and serum creatinine, which were used to create survival matrices for 3- and 5-year OS. The model was internally and externally validated using Connect MM Cohort 2 (Harrell's concordance index, 0·698), MM-015 (0·649), and the phase 3 FIRST (0·647) clinical trials. This novel prognostic tool may help inform outcomes for NDMM in the era of triplet therapy use with novel agents.

Stage I-III colon cancer patients with tumor deposits behave similarly to stage IV patients. Cross-section analysis of 392 patients.

BACKGROUND AND OBJECTIVES: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colorectal cancer. However, controversy exists regarding their definition, evaluation, and staging categories. This study aimed to determine the survival and recurrence impact of the TD in colon adenocarcinomas; and to determine if TD patients behave similarly to stage IV patients. METHODS: Cross-section study from 392 patients with colon adenocarcinoma from 2005 to 2012. We performed survival analysis and further stratified patients considering TD patients as a "stage IV-TD" to demonstrate if they behave similarly than stage IV patients. RESULTS: From 392 patients, 204 (52%) were men, the mean age was 57.4 ± 13.9 years and 11.5% of cases had TD. In a multivariate analysis, TD failed to predict mortality and recurrence. Considering cases with TD as stage IV-TD, their mean survival was similar to stage IV patients (69.3 and 64.6 months, respectively) and different to those in stage III (110.5 months), II (135.7 months), and I (114.9 months) (P < 0.001). CONCLUSIONS: TD failed to predict mortality and recurrence. Patients with TD in stage I-III shows similar mortality than stage IV patients; then, we suggest putting them into a substage IV category instead of the N1c category.

Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization.

The seven APOBEC3 (A3) enzymes in primates restrict HIV/SIV replication to differing degrees by deaminating cytosine in viral (-)DNA, which forms promutagenic uracils that inactivate the virus. A polymorphism in human APOBEC3C (A3C) that encodes an S188I mutation increases the enzymatic activity of the protein and its ability to restrict HIV-1, and correlates with increased propensity to form dimers. However, other hominid A3C proteins only have an S188, suggesting they should be less active like the common form of human A3C. Nonetheless, here we demonstrate that chimpanzee and gorilla A3C have approximately equivalent activity to human A3C I188 and that chimpanzee and gorilla A3C form dimers at the same interface as human A3C S188I, but through different amino acids. For each of these hominid A3C enzymes, dimerization enables processivity on single-stranded DNA and results in higher levels of mutagenesis during reverse transcription in vitro and in cells. For increased mutagenic activity, formation of a dimer was more important than specific amino acids and the dimer interface is unique from other A3 enzymes. We propose that dimerization is a predictor of A3C enzyme activity.

A Single Nucleotide Polymorphism in Human APOBEC3C Enhances Restriction of Lentiviruses.

Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution. Here, we describe a single nucleotide polymorphism in human APOBEC3C, a change from serine to isoleucine at position 188 (I188) that confers potent antiviral activity against HIV-1. The gain-of-function APOBEC3C SNP results in increased enzymatic activity and hypermutation of target sequences when tested in vitro, and correlates with increased dimerization of the protein. The I188 is widely distributed in human African populations, and is the ancestral primate allele, but is not found in chimpanzees or gorillas. Thus, while other hominids have lost activity of this antiviral gene, it has been maintained, or re-acquired, as a more active antiviral gene in a subset of humans. Taken together, our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses.

Impact of post-transplantation maintenance therapy on health-related quality of life in patients with multiple myeloma: data from the Connect® MM Registry.

Maintenance therapy after autologous stem cell transplantation (ASCT) is recommended for use in multiple myeloma (MM); however, more data are needed on its impact on health-related quality of life (HRQoL). Presented here is an analysis of HRQoL in a Connect MM registry cohort of patients who received ASCT ± maintenance therapy. The Connect MM Registry is one of the earliest and largest, active, observational, prospective US registry of patients with symptomatic newly diagnosed MM. Patients completed the Functional Assessment of Cancer Therapy-MM (FACT-MM) version 4, EuroQol-5D (EQ-5D) questionnaire, and Brief Pain Inventory (BPI) at study entry and quarterly thereafter until death or study discontinuation. Patients in three groups were analyzed: any maintenance therapy (n = 244), lenalidomide-only maintenance therapy (n = 169), and no maintenance therapy (n = 137); any maintenance and lenalidomide-only maintenance groups were not mutually exclusive. There were no significant differences in change from pre-ASCT baseline between any maintenance (P = 0.60) and lenalidomide-only maintenance (P = 0.72) versus no maintenance for the FACT-MM total score. There were also no significant differences in change from pre-ASCT baseline between any maintenance and lenalidomide-only maintenance versus no maintenance for EQ-5D overall index, BPI, FACT-MM Trial Outcomes Index, and myeloma subscale scores. In all three groups, FACT-MM, EQ-5D Index, and BPI scores improved after ASCT; FACT-MM and BPI scores deteriorated at disease progression. These data suggest that post-ASCT any maintenance or lenalidomide-only maintenance does not negatively impact patients' HRQoL. Additional research is needed to verify these findings.

Idiopathic Granulomatous Mastitis: Manifestations at Multimodality Imaging and Pitfalls.

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast entity characterized by lobulocentric granulomas. IGM has a persistent or recurrent disease course and affects parous premenopausal women with a history of lactation. It has also been associated with hyperprolactinemia. The most common clinical sign is a palpable tender mass. However, the nonspecific manifestations and varied demographic features of this condition, as well as the other similar-appearing and superimposed breast entities, pose substantial diagnostic challenges. Entities with similar manifestations include inflammatory breast cancer (IBC), infective mastitis, foreign body injection granulomas, mammary duct ectasia, diabetic fibrous mastopathy, and systemic granulomatous processes. The strategy for imaging IGM depends on patient age, clinical manifestations, and risk factors. Targeted ultrasonography, mammography, and less commonly, magnetic resonance imaging have proven to be useful for imaging evaluation. Core-needle biopsy, with or without fine-needle aspiration for cytopathologic examination, and culture analysis are usually required to exclude IBC and other benign inflammatory breast processes. Patients with IGM have an excellent prognosis when they are appropriately treated with oral steroids or second-line immunosuppressive and prolactin-lowering medications. However, surgical excision may be an option for patients in whom medication therapy is unsuccessful. Imaging surveillance can be offered to patients with incidentally encountered IGM or mild symptoms. Clinical suspicion for this rare disease and the breast imager's prompt diagnosis can lead to an improved patient outcome. The purpose of this article is to review the imaging manifestations of IGM in a multimodality case-based format and to describe relevant clinical and imaging-based differential diagnoses. The associated pitfalls, epidemiologic and histopathologic factors, clinical manifestations, natural course, and management of IGM also are discussed. ©RSNA, 2018.

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a modality of cancer treatment in which tumor cells are destroyed by reactive oxygen species (ROS) produced by photosensitizers following its activation with visible or near infrared light. The PDT success is dependent on different factors namely on the efficiency of the photosensitizer deliver and targeting ability. In this review a special attention will be given to the role of some drug delivery systems to improve the efficiency of tetrapyrrolic photosensitizers to this type of treatment.

Obesity as a Presentation of Munchausen Syndrome by Proxy.

Objective: To describe a case of an obese child whose weight gain was related to the Munchausen Syndrome by proxy (MSP). Methods: This is a case report including information regarding the child's clinical history and the mother's behavior. The common features of the syndrome are confronted with the description of the case, seeking to demonstrate the similarities. Results: The description ratifies the diagnosis based on the signs and symptoms presented by the child (<5 years old, frequent contacts with health system, symptoms witnessed only by the mother, confusing findings, not helped by treatments, emotionally distant father) and the attitude of the mother (concerned, interested in procedures, comfortable in the medical setting, higher medical knowledge, hostile when thwarted). Conclusion: The case presented points to a new etiology, the MSP, to be considered within the set of factors currently known to cause and maintain obesity in childhood.

Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution.

LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host-pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE-1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated.